Clinically, exogenous estrogens are used therapeutically in dysmenorrhea, menopausal disorders, prostatic hypertrophy, and linear growth disfunction, but are contraindicated in pregnancy, and in individuals with histories of neoplastic, diabetic or cardiovascular disorders. Using physiologic and pharmacologic doses of delta 9-tetrahydrocannabinol (THC) and/or estradiol benzoate (EB), studies under our present grant (#1 RO1 DA 01176 01) demonstrate that: 1) THC alone has significant (P less than 0.001) estrogen-like activities in adult male and spayed female rats; as measured by depressed seminal vescile and increased adrenal weights; depressed somatic growth and uterine weight and vaginal smears bioassays; 2) in pregnant rats, THC may influence fetal genital development; 3) in male neonates, THC significantly (P less than 0.001) inhibits EB action on testes, seminal vesicle and ventral prostate weights. We wish to continue our studies on the mechanism(s) by which THC exerts estrogenic and anti-androgenic activities during rat male and female growth and development. Since THC and EB act directly on reproductive tissue, and indirectly via the CNS, we plan to compare the direct effects of EB and/or THC on male and female reproductive tract histochemistry; and uterine and testicular RNA polymerase activity. Indirect effects of EB and THC will be studied by examining the effect of these compounds on brain 5-HT content, and reproductive behavior. In sum: work in this and other laboratories demonstrates that marihuana has estrogenic and anti-androgenic activity in humans and rodents; studies on the mechanisms by which THC inhibits or exerts estrogen-like-activity in rat development and growth are of interest where marihuana use may be of significance where estrogen administration is either clinically prescribed or proscribed.